The research program involves the biochemical and physiological study of a new polypeptide hormone, epidermal growth factor (EGF) isolated from the submaxillary glands of mice. Mouse EGF is a 53 residue, single chain polypeptide, containing 3 disulfide bonds. The amino acid sequence has been determined. EGF stimulates epidermal proliferation both when administered to newborn animals and in organ culture of chick embryo skin. It also stimulates the growth of corneal epithelium when applied topically to wounded corneas of rabbits, and in corneal organ cultures of chick embryos and human fetuses. Finally, EGF is a potent mitogen for human fibroblasts in culture. We have recently been able to isolate the human counterpart of EGF from protein concentrates of human urine. The amino acid compositions of the human and mouse polypeptides differ, although certain similarities are present. Both polypeptides compete for the same site on the cell membrane, and both polypeptides have identical biological effects in cell cultures and in the intact animal. The metabolic fate of both mouse and human EGF is being studied using 125I-labeled material. The binding of the labeled hormone to the fibroblast membrane and the metabolic consequences of the binding will be examined. Our general approach to the problem has been to try to understand the normal role of EGF in the organism, to define its function in cell growth and development, and to understand the biochemical basis for the growth stimulating properties of this new hormone. BIBLIOGRAPHIC REFERENCES: Carpenter, G. and Cohen, S., Human Epidermal Growth Factor and the Proliferation of Human Fibroblasts. J Cell Physiol., 88: 227, 1976. Carpenter, G. and Cohen, S., 125I-labeled Human Epidermal Growth Factor: Binding, Internalization, and Degradation in Human Fibroblasts. J. Cell Biology, 71: 159, 1976.